Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are RNA binding proteins that posttranscriptionally regulate the expression of mRNAs coding for proteins involved in the maintenance of iron and energy homeostasis. The RNA binding activities of the IRPs are regulated by changes in cellular iron. Thus, the IRPs are considered iron sensors and the principle regulators of cellular iron homeostasis. The mechanisms governing iron regulation of the IRPs are well described. Recently, however, much attention has focused on the regulation of IRPs by reactive nitrogen and oxygen species (RNS, ROS). Here we focus on summarizing the iron-regulated RNA binding activities of the IRPs, as well as the recent findings of IRP regulation by RNS and ROS. The recent observations that changes in oxygen tension regulate both IRP1 and IRP2 RNA binding activities will be addressed in light of ROS regulation of the IRPs.
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PMID:Regulation of the iron regulatory proteins by reactive nitrogen and oxygen species. 1044 Feb 37

Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making their identification very difficult as a specific cause of neurodegeneration. Recently, we have developed a high performance liquid chromatography/electrochemical detection (HPLC/EC) method to identify 3-nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite production, in cell cultures and brain to evaluate if an agent-driven neurotoxicity is produced by the generation of peroxynitrite. We show that a single or multiple injections of methamphetamine (METH) produced a significant increase in the formation of 3-NT in the striatum. This formation of 3-NT correlated with the striatal dopamine depletion caused by METH administration. We also show that PC12 cells treated with METH has significantly increased formation of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with antioxidants such as selenium and melatonin can completely protect against the formation of 3-NT and depletion of striatal dopamine. We also report that pretreatment with peroxynitrite decomposition catalysts such as 5, 10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20-tetrakis (2,4,6-trimethyl-3,5-sulfonatophenyl) porphinato iron III (FETPPS) significantly protect against METH-induced 3-NT formation and striatal dopamine depletion. We used two different approaches, pharmacological manipulation and transgenic animal models, in order to further investigate the role of peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of 3-NT as well as striatal dopamine depletion. Similar results were observed with nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed transgenic mice models. Finally, using the protein data bank crystal structure of tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine moiety in the enzyme that can be responsible for dopaminergic neurotoxicity. Together, these data clearly support the hypothesis that the reactive nitrogen species, peroxynitrite, plays a major role in METH-induced dopaminergic neurotoxicity and that selective antioxidants and peroxynitrite decomposition catalysts can protect against METH-induced neurotoxicity. These antioxidants and decomposition catalysts may have therapeutic potential in the treatment of psychostimulant addictions.
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PMID:Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts. 1146 92

Exposure to asbestos causes cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The pathogenesis of asbestos-related diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibers generate reactive oxygen and nitrogen species (ROS/RNS) and cause oxidation and/or nitrosylation of proteins and DNA. The ionic state of iron and its ability to be mobilized determine the oxidant-inducing potential of pathogenic iron-containing asbestos types. In addition to their capacity to damage macromolecules, oxidants play important roles in the initiation of numerous signal transduction pathways that are linked to apoptosis, inflammation, and proliferation. There is strong evidence supporting the premise that oxidants contribute to asbestos-induced lung injury; thus, strategies for reducing oxidant stress to pulmonary cells may attenuate the deleterious effects of asbestos.
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PMID:Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases. 1270 92

NO or its derivatives (reactive nitrogen species, RNS) inhibit mitochondrial complex I by several different mechanisms that are not well characterised. There is an inactivation by NO, peroxynitrite and S-nitrosothiols that is reversible by light or reduced thiols, and therefore may be due to S-nitrosation or Fe-nitrosylation of the complex. There is also an irreversible inhibition by peroxynitrite, other oxidants and high levels of NO, which may be due to tyrosine nitration, oxidation of residues or damage of iron sulfur centres. Inactivation of complex I by NO or RNS is seen in cells or tissues expressing iNOS, and may be relevant to inflammatory pathologies, such as septic shock and Parkinson's disease.
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PMID:Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. 1528 73

Inhaled fibres with certain physico-chemical properties are known to induce mesothelioma in humans. The induction of reactive oxygen (ROS) or nitrogen species (RNS) have been suggested as molecular mechanism of fibre induced carcinogenesis. In earlier studies we were able to demonstrate that crocidolite asbestos in vivo induces mutations in transgenic rats with a specific molecular spectrum that indicates the involvement of 8-hydroxydeoxyguanosine (8-OHdG) as pre-mutagenic adduct. 8-OHdG may be induced by primary (direct) and/or secondary (cellular mediated) mechanisms. Therefore, the induction of 8-OHdG as well as the inflammatory response of animals treated with fibre samples significantly differing in their physico-chemical characteristics was investigated. As appropriate system to study mesothelioma carcinogenesis, intraperitoneal injection in rats was used with samples of UICC crocidolite, crocidolite with reduced iron content, and a vitreous fibre (MMVF 11). Equal numbers of carcinogenic fibres from each sample revealed significant comparable increases in 8-OHdG induction. Parameters of inflammation (percentage of macrophages and TNF-alpha secretion) correlated significantly with the induction of 8-OHdG, 10 weeks after treatment.
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PMID:Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats. 1528 33

Nitric oxide and NO-derived species (RNS) are defence molecules with broad antimicrobial activity. Microorganisms have developed strategies to sense RNS and counteract their damaging effects. We used Saccharomyces cerevisiae, harbouring a deletion of YHB1 that encodes the main NO scavenger enzyme, to study consequences of RNS exposure on whole-genome transcriptional response. The expression of > 700 genes was altered on RNS treatment. No major role for ROS-scavenging enzymes was found, and the respiratory chain, the main site of ROS production, had only minor involvement in the RNS-induced stress. The changes were generally transient and also found after treatment with the respiratory inhibitor myxothiazol. However, 117 genes showed a persistent response that was not observed after myxothiazol treatment. Of these, genes of the glutathione and DNA repair systems, iron homeostasis and transport were found to be upregulated. Severe repression of genes of respiratory chain enzymes was observed. Many of these genes are known to be regulated by the transcription factor Hap1p, suggesting that RNS might interfere with Hap1p activity. We showed also that Msn2/4p and Yap1p, key regulators of the response to general stress and oxidative stress, respectively, played a role in mediating the RNS-induced response.
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PMID:Transcriptional response to nitrosative stress in Saccharomyces cerevisiae. 1671 Aug 43

A great body of experimental evidence collected over many years indicates that calcium has a central role in a variety of neuronal functions. In particular, calcium participates in synaptic plasticity, a neuronal process presumably correlated with cognitive brain functions such as learning and memory. In contrast, only recently, evidence has begun to emerge supporting a physiological role of reactive oxygen (ROS) and nitrogen (RNS) species in synaptic plasticity. This subject will be the central topic of this review. The authors also present recent results showing that, in hippocampal neurons, ROS/RNS, including ROS generated by iron through the Fenton reaction, stimulate ryanodine receptor-mediated calcium release, and how the resulting calcium signals activate the signaling cascades that lead to the transcription of genes known to participate in synaptic plasticity. They discuss the possible participation of ryanodine receptors jointly stimulated by calcium and ROS/RNS in the normal signaling cascades needed for synaptic plasticity, and how too much ROS production may contribute to neurodegeneration via excessive calcium release. In addition, the dual role of iron as a necessary, but potentially toxic, element for normal neuronal function is discussed.
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PMID:A role for reactive oxygen/nitrogen species and iron on neuronal synaptic plasticity. 1711 37

In experiments in vivo we studied the interaction between two ion-transporting mechanisms of cardiovascular system--Na+, K+ -ATPase of rat aorta and Ca2+ -uptake system of mitochondria in short-term response to different doses of NO donor, nitroglycerine (NG). The activity of the Na+, K+ -ATPase was determined in rat aorta, and mitochondrial uptake of Ca2+ was studied in rat heart mitochondria assuming that metabolism induced by NO in cardiac mitochondria is similar to that in rat aortic mitochondria. The data show a coordinated dose-dependent action of NG on Na+, K+ -ATPase activity as well as Ca2+ -uptake in mitochondria. An activation of Na+, K+ -ATPase by low dose of NG (0.25 mg/kg body weight) is accompanied by the activation of Ca2+ -uptake in mitochondria as a result of inhibition of permeability transition pore. However, further increase of the dose of the drug leads to reciprocal changes of studied parameters: the decrease in Na+ -pump activity below the control level and the increase of Ca2+ -uptake in mitochondria with a peak at 1.0 mg/kg NG, which takes place in parallel with the dramatic rise in the level of ROS and RNS together with their toxic products, nitrosothiols (NT) and free iron (Fe2+) content in mitochondria. Strong correlation between Ca2+ -uptake and Fe2+ -release, Fe2+ -release and OH-radical formation, the rise in OH-radical level and the decrease of that of H2O2 and mitochondrial NT together with the inhibition of Na+, K+ -ATPase favor a hypothesis that oxidative stress in rat aorta is of mitochondrial origin due to an enhanced uptake of Ca2+ into mitochondrial matrix, Fe2+ deliverance and manifold increase in OH-radical formation from decomposition of hydroperoxide in Haber-Weiss reaction and the decomposition of mitochondrial NT via formation of peroxynitrite, both catalysed by Fe2+, with subsequent release of *OH-radical. Effective abolition of Na+, K+ -ATPase inhibition by potent antioxidant melatonine gives the evidence of the oxidative nature of Na+, K+ -ATPase inhibition by nitric oxide in rat aorta.
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PMID:[The role of mitochondria in NO-dependent regulation of Na+, K+ -ATP activity in the rat aorta]. 2096 40

Despite the crucial role of redox active metals like copper and iron in central biological reactions, their elevated levels are involved in the pathogenesis of Alzheimer's Disease (AD). Similarly reactive oxygen/nitrogen species (ROS/RNS) produced during normal metabolic activities, specifically oxidative phosphorylation of the cell, are scavenged by antioxidant enzymes like superoxide dismutase (SOD), catalase but impaired metabolic pathways tend to generate elevated levels of these ROS/RNS. Iron, copper, and zinc are some of the metals, which intensify this process and contribute for the pathogenesis of AD. This review summarizes the mechanism of ROS/RNS production and their role in lipid peroxidation. The factors, which make brain vulnerable for lipid peroxidation, have been discussed. It also focuses on possible treatment options and future directions.
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PMID:Lipid peroxidation in Alzheimer's disease: emphasis on metal-mediated neurotoxicity. 2130 49

Some aspects of reactive nitrogen and oxygen species (RNS and ROS) metabolism in rat heart mitochondria under administration of different doses of nitroglycerine (NG) in vivo are discussed. It is shown that NG administration results in a dose-dependent increase in Ca2+-uptake in mitochondria, due to the dose-dependent inhibition of mitochondrial permeability transition pore (MPTP) in vivo and the activation of Ca2+-dependent mitochondrial NOS. It was shown that NOS activity increases in accord with the increase of Ca2+-uptake in mitochondria. The dose-dependent activation of nitratreductase is observed. However, nitrite production decreases dose-dependently, according to the change of NO2-/NO3- ratio on behalf of NO3-, the end product of NO transformations. The relation between nitrosylation of mitochondrial proteins with the nitrosothiols formation and nitrate production also changes towards NO3-, which shows the activation of oxidation reactions in heart mitochondria after NG administration. Accordingly, dose-dependent increase in lipid peroxidation (LP) products is shown, the hallmark of the membrane damage in mitochondria. It is established that the cause of oxidative stress, besides the dose-dependent increase in ROS production (hydroperoxide, superoxide and hydroxyl-radical), lies in the increase of free iron content, derived from the oxidation of mitochondrial iron-containing proteins. The iron interaction with hydroperoxide following Fenton reaction as well as free-radical decomposition ofperoxynitrite, derived from NO3- are the possible cause of manifold increase in ROS as well as LP production, and RNS oxidation to NO3-. Thus, NO-dependent MPTP blockage, due to NO synthesis in mitochondria in vivo, results in the activation of both constituents of NO-cycle: NOS-dependent, due to Ca2+-dependent activation of mitochondrial NOS, and nitrate-reductase-dependent, due to the increase in NO3- formation. However, increase in ROS production, augmented by the iron release, leads to the oxidative stress and the shift of RNS metabolism towards NO3- formation, in spite of the activation of nitrate-reductase-dependent pathway of NO-cycle. It is shown that reversible MPTP opening in vitro diminishes ROS production, whereas MPTP blockage by cyclosporine A restores the ROS formation to control level. Thus, MPTP-dependent inhibition of ROS overproduction both in vitro and in vivo, shows the importance of MPTP in the regulation of ROS and RNS metabolism in mitochondria.
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PMID:[Reactive nitrogen and oxygen species metabolism in rat heart mitochondria upon administration of NO donor in vivo]. 2287 47


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